The advantages of controlled release products are well known in the pharmaceutical field and include the ability to maintain a desired blood level of a medicament over a comparatively longer period of time while increasing patient compliance by reducing the number of administrations necessary to achieve the same. These advantages have been attained by a wide variety of methods.
Oral controlled release delivery systems should ideally be adaptable so that release rates and profiles can be matched to physiological and chronotherapeutic requirements. While many oral controlled and sustained release formulations are already known, certain drugs that are relatively insoluble in water and which further have relatively high dose requirements (based on weight) present formulation difficulties which render them unsuitable for inclusion in sustained release formulations. Difficulties in preparing suitable sustained release formulations of insoluble drugs are increased when the dose of the insoluble drug to be delivered to render a therapeutic effect over the desired period of time is relatively high, e.g., 500 mg or greater.
An example of a high dose, insoluble drug is ibuprofen, which is a non-steroidal anti-inflammatory agent ("NSAID"). Several immediate release forms of ibuprofen are commercially available, e.g., Motrin.RTM. (available from Upjohn) and Brufen.RTM. (available from The Boots Company PLC), and a sustained release ibuprofen formulation, Brufen Retard.TM., is commercially available from the Boots Company PLC. Indomethacin, another high dose insoluble NSAID, is commercially available in sustained release form as Indocin SR.TM. from Merck & Co., Inc.
There is still a need in the art for sustained release dosage forms of insoluble NSAIDs that are bioavailable and provide suitable release profiles of the NSAID from the dosage form over a sustained period of time, e.g. for about 12 to about 24 hours.